April 2011

Hard Decisions — Ultrasound Elastography Seeks to Help Characterize Breast Lesions and, More Recently, Throughout the Body
By Beth W. Orenstein
Radiology Today
Vol. 12 No. 4 P. 26

Interest in ultrasound elastography’s utility in measuring the stiffness of tissue is increasing. Elastography is a software add-on to ultrasound equipment and has been available since the 1990s. It helps physicians characterize lesions based on the well-established observation that malignant lesions are almost always stiff, while benign lesions are softer.

Elastography has shown the most promise, and today is most often used to help differentiate benign from malignant breast lesions. It is also being studied as an imaging tool for evaluating lesions and disease in other soft tissue organs such as the thyroid, liver, kidneys, and prostate as well as for musculoskeletal conditions. Researchers are looking at using elastography to evaluate the age of deep vein thromboses. Older clots, which need to be treated differently than newer ones, may be stiffer.

At RSNA 2005, Richard G. Barr, MD, PhD, of Northeastern Ohio Universities College of Medicine in Rootstown and Radiology Consultants, Inc in Youngstown, reported having high sensitivity and high specificity for determining whether a breast lesion was benign or malignant with elastography. “Since then the technology has continued to improve,” he says, and it’s now a routine part of breast ultrasounds in his practice. (The FDA approved the technology in 2006.)

Also at RSNA 2005, Barr and his colleagues reported their success in evaluating breast lesions with strain elastography. “With strain imaging,” he explains, “we apply a small amount of pressure to the breast or organ and look to see how that little bit of pressure causes a change.”

The researchers found that breast cancers were not only hard but also appeared larger on the elastogram, while benign lesions, which are soft, appeared smaller.
“It was those size changes that we used to get the high sensitivity and high specificity for determining whether a lesion was benign or cancer,” he says.

Shear Wave
Multiple manufacturers, including Siemens, Philips, GE, and Toshiba, offer this elastography software, Barr says. In addition, a company based in Aix-en-Provence, France, SuperSonic Imagine, has developed another elastography technology, which was approved by the FDA in 2009, called ShearWave Elastography.

SuperSonic’s Aixplorer uses two types of waves: an ultrasound wave that creates a high-quality B-mode image and a shear wave that can be measured as it propagates in tissue, rendering a quantitative, color-coded map of tissue stiffness, says Cofounder and Chief Scientific Officer Claude Cohen-Bacrie, who had worked in ultrasound for Philips in the United States for many years before returning to France.

Shear wave elastography is a reproducible technology that assesses the stiffness of tissue in kilopascals, a unit of pressure. The propagation speed of a shear wave is faster in harder tissues. Barr says he particularly likes that the shear wave elastography technique provides a specific number that corresponds to a tissue’s firmness.

At the European Congress of Radiology in March, SuperSonic Imagine released the results of its global multicenter study that was conducted at 17 U.S. and European sites. The study showed that when its shear wave elastography is combined with sonography, it improves Breast Imaging Reporting and Data System (BI-RADS) classifications, particularly for distinguishing between BI-RADS 3 and 4, which can be problematic. (BI-RADS 2 indicates a suspect area is benign, and 5 is highly suggestive of malignancy.)

“The study showed that improved classification with ShearWave Elastography would correctly classify lesions that are probably benign in the BI-RADS 3 category, reducing the rate of invasive procedures or negative biopsies,” Cohen-Bacrie says. “Correct classification would also mean that some lesions would be moved from a BI-RADS 3 to a BI-RADS 4, reaching a positive biopsy faster for a given lesion and therefore reducing the risk of a late diagnosis for aggressive cancers.”

Launched in June 2008, SuperSonic’s investigative study involving 1,800 patients with breast lesions also showed that the results of its shear wave elastography are highly reproducible both quantitatively and qualitatively, Cohen-Bacrie says.

Having used both technologies—strain elastography, which measures tissue displacement, and ShearWave, which quantifiably measures tissue stiffness—Barr finds they are complementary. “Using both together actually helps us and I think will improve the sensitivity and specificity even more from what we had from each individual study,” he says.

BI-RADS Classification
By routinely using elastography in its practice for the last five years or so, Barr says he and his colleagues have reduced the number of biopsies they recommend by about one-third to one-half.

“Where we find it most helpful is in the BI-RADS 3 and BI-RADS 4A, lesions where there are low probabilities for malignancies,” Barr says. “We allow elastography to sway us to just watching vs. doing a biopsy in those cases.”

He adds that elastography is becoming “more and more accepted as a breast imaging technology” and that he expects it to soon be added to the ACR’s BI-RADS classification system. However, Barr notes that having excellent B-mode is still critical for breast ultrasound.

Barr will soon publish a paper on an additional phenomenon he sees on elastograms that help him better distinguish benign and malignant cystic breast lesions. He has found that when using Siemens ultrasound equipment, if he sees a bull’s-eye artifact, it’s more likely the lesion is benign. Of the 383 lesions he studied, 243 (63.4% biopsy rate) were recommended for biopsy based on their B-mode characteristics. Of the 243 lesions, 62 demonstrated the bull’s-eye artifact on elastography images, and all were confirmed benign cysts on pathology. Of the 181 lesions without the artifact, 116 were benign noncystic lesions, and 65 were malignant noncystic lesions.

“Hence, within the biopsied lesions, the bull’s-eye artifact had perfect sensitivity, specificity, and positive predictive value in determining pathologically proven benign cysts,” Barr says, adding that looking for the bull’s-eye artifact could further reduce unnecessary biopsies. 

Julia Dmitrieva, applications product manager for women’s healthcare/ultrasound for Philips Healthcare, believes that while extensive evidence exists in the literature about how helpful elastography is in diagnosing breast tumors and assisting in biopsies, more research is needed.

“There is research that shows elastography could be helpful in determining benign vs. malignant, but not all malignant tumors are hard,” she says. “There are soft malignant tumors as well. That’s why it’s really interesting for the healthcare community to continue to research and see the benefits that elastography could add in raising diagnostic confidence.”

Elastography is a great tool in the imaging toolbox, Dmitrieva adds, but it’s not the only imaging technique. “Guidelines suggest a multimodality approach to comprehensive screening, diagnosis, and management of breast disease,” she says. “Physicians have discovered the value of multiple imaging modalities in creating a more complete picture of disease.”

As with all sonography, says Sonja Rothfuss, marketing manager for women’s healthcare/ultrasound for Philips, the operator’s technique can affect image quality and thus the exam results. Rothfuss says that when adding features such as elastography, Philips considered ease of use and reproducibility.

“We listened to our customers and made something that is very easy to use,” she says. “Users push one button and get an elastogram in addition to the B-mode images. There is virtually no external compression required since Philips’ technique triggers from respiration and cardiac motion of the patient, which increases the reproducibility between exams and users.” Philips received FDA approval for its elastography technology in breast imaging in 2010.

Other Applications
Researchers are finding applications for elastograms in gynecological, prostate, musculoskeletal, abdomen, liver, and thyroid imaging. Of those, liver and thyroid may be the most advanced.

Several studies have shown that elastograms can be used to determine the amount of fibrosis within the liver. “At the present time, patients who have cirrhosis are getting serial biopsies to see if there is any improvement or progression of the disease,” Barr says. “With elastography technology, it could be possible that we would not have to do those biopsies.”

Elastography may also prove useful when it comes to liver masses. Acquiring good elastograms of masses in the liver is more difficult than acquiring images of those in the breast because the patient is breathing, “and the motion is too high or too much to get good images,” Barr says. “We have to have the patient hold his breath, and we’re still working out some of the technical details.”

Also, liver lesions are deeper in the body, Barr says, “and you suffer from loss of sensitivity with sonography as you get deep within the lesion, deeper than 6 or 7 cm. That goes for everything in the abdomen and pelvis—kidneys, pancreas, etc. There is a lot of work going on to try to overcome the technical problems of doing elastogram studies, and we’re not there yet.”

Using elastography for examining liver fibrosis is more common in Europe than the United States. The Aixplorer with elastography for the liver is approved in the United States without the quantification tool, Cohen-Bacrie notes. He says that in addition to ShearWave Elastography, the Aixplorer offers contrast imaging (outside the United States), which enables a better visualization and characterization of liver focal lesions such as cancers and metastasis.

Another area where Barr sees potential is thyroid imaging. “Our personal experience is that the strain imaging has not been that helpful in terms of deciding whether a lesion is benign or malignant, but with shear wave imaging, where we get an absolute number corresponding to the hardness of the lesion, we think it will prove very helpful in determining whether a lesion is benign or malignant. There is a huge potential for decreasing the number of thyroid biopsies. It’s not as mature as with the breast yet, but it’s a really hot area. People are working on it—it’s not prime time yet, but it’s going to be another area where it is going to make a huge clinical impact once we get more data.”

According to Cohen-Bacrie, the shear wave elastography technique without compression is particularly well adapted to the thyroid gland and could be helpful in complementing gray scale for the assessment of nodules that could remain ambiguous after fine-needle aspiration (FNA) and for lymph node follow-up. However, he says, whether it will decrease the number of systematic thyroid FNAs remains an open question that will require further clinical study.

The use of sonography for musculoskeletal imaging (eg, muscles, tendons, ligaments, joints, soft tissue), long popular in Europe, is growing in the United States as well. Shear wave elastography provides a quantitative assessment, in kilopascals, of changes in muscle and tendon tissue stiffness, Cohen-Bacrie says. “Thus, it would be valuable to study its usefulness in characterizing abnormal tissue and small local injuries as well as monitoring changes after therapy or surgery,” he says.

Prostate Imaging
Prostate is yet another area where elastography shows promise, Barr says. That it has potential with the prostate is wonderful, he says, because “there’s nothing we do now with the prostate that works very well.”

Cohen-Bacrie says shear wave elastography can help guide biopsies of the prostate by offering complementary information to gray-scale ultrasound. “You can now supplement systematic biopsies of the prostate by targeting different areas of stiffness in the gland. The clinical question that remains to be proven is, ‘Will this technology improve the positive biopsy rate in the prostate?’” he says.

Researchers are also looking at elastography for imaging other abdominal anatomy, including the kidney, gallbladder, pancreas, bladder, pelvis, and spleen. “Researchers are using the Aixplorer to assess the rejection of kidney transplants,” Cohen-Bacrie says.

Research also suggests that the stiffness of a blood clot may be related to its age, and using elastography techniques may allow researchers to determine the age of a deep vein thrombosis, as knowing whether a clot is acute or chronic is important in determining the proper treatment.

— Beth W. Orenstein is a freelance medical writer based in Northampton, Pa. She is a frequent contributor to Radiology Today.